Tanshinone IIA promotes non-amyloidogenic processing of amyloid precursor protein in platelets via estrogen receptor signaling to phosphatidylinositol 3-kinase/Akt

丹参酮IIA通过雌激素受体信号通路激活磷脂酰肌醇3-激酶/Akt信号通路,促进血小板中淀粉样前体蛋白的非淀粉样生成加工。

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Abstract

Amyloid β peptide (Aβ) is a proteolytic product of amyloid precursor protein (APP). Recent findings suggested that platelet-derived Aβ is closely associated with the pathogenesis of atherosclerosis (AS). Tanshinone IIA (Tan IIA), a pharmacologically active component of the Chinese herb Salvia miltiorrhiza Bunge, has long been used to treat AS and was also identified as a phytoestrogen. However, it has not been elucidated whether Tan IIA intervenes with platelet APP processing and whether such an intervention is associated with its estrogenic activity. Using human platelets, this study demonstrated that Tan IIA promoted the non-amyloidogenic cleavage of APP via estrogenic activity. The phosphatidylinositol 3-kinase/Akt pathway may be involved in this effect of Tan IIA on platelet APP metabolism as a downstream effector of estrogen receptor signaling. This study aimed to extend the existing data and provide new insights into the mechanism underlying the vasoprotective effect of Tan IIA.

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